Development of the Respiratory System

Overview

Lung development occurs in 5 stages:

• Embryonic: development of the trachea Trachea The trachea is a tubular structure that forms part of the lower respiratory tract. The trachea is continuous superiorly with the larynx and inferiorly becomes the bronchial tree within the lungs. The trachea consists of a support frame of semicircular, or C-shaped, rings made out of hyaline cartilage and reinforced by collagenous connective tissue. Trachea: Anatomy and primary bronchial buds
• Pseudoglandular: development of the bronchial tree Bronchial tree The collective term “bronchial tree” refers to the bronchi and all of their subsequent branches. The bronchi are the airways of the lower respiratory tract. At the level of the 3rd or 4th thoracic vertebra, the trachea bifurcates into the left and right main bronchi. Both of these bronchi continue to divide into secondary or lobar bronchi that bifurcate further and further. Bronchial Tree: Anatomy down to the level of the terminal bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy
• Canalicular: development of the respiratory bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy and primitive alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS)
• Saccular: maturation of the alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) and production of surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS)
• Alveolar: increase in number of alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS), capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology, and continued maturation

In utero, the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy are:

• Unnecessary as breathing organs (they are dormant)
• A primary source of amniotic fluid Amniotic fluid A clear, yellowish liquid that envelopes the fetus inside the sac of amnion. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (amniocentesis). Placenta, Umbilical Cord, and Amniotic Cavity 
• Filled with fluid and not inflated

Immediately following delivery:

• Lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy expand for the first time with a baby’s 1st breath.
• This 1st breath pushes amniotic fluid Amniotic fluid A clear, yellowish liquid that envelopes the fetus inside the sac of amnion. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (amniocentesis). Placenta, Umbilical Cord, and Amniotic Cavity out of the airspaces and into the vasculature as lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy fill with air.
• Surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) ↓ surface tension Surface tension The force acting on the surface of a liquid, tending to minimize the area of the surface. Acute Respiratory Distress Syndrome (ARDS) in the alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) and keeps air spaces open.
• Adequate surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) is often a primary factor in determining infant survival.

Mnemonic:

To quickly recall the chronology of the stages of lung development, remember “Every Pulmonologist Can See Alveoli”:

• Embryonic
• Pseudoglandular
• Canalicular
• Saccular
• Alveolar

Embryonic Stage

Development of the bronchial tree Bronchial tree The collective term “bronchial tree” refers to the bronchi and all of their subsequent branches. The bronchi are the airways of the lower respiratory tract. At the level of the 3rd or 4th thoracic vertebra, the trachea bifurcates into the left and right main bronchi. Both of these bronchi continue to divide into secondary or lobar bronchi that bifurcate further and further. Bronchial Tree: Anatomy begins in the embryonic stage, with budding Budding Mycology of the embryonic gut tube to form the larynx Larynx The larynx, also commonly called the voice box, is a cylindrical space located in the neck at the level of the C3-C6 vertebrae. The major structures forming the framework of the larynx are the thyroid cartilage, cricoid cartilage, and epiglottis. The larynx serves to produce sound (phonation), conducts air to the trachea, and prevents large molecules from reaching the lungs. Larynx: Anatomy, trachea Trachea The trachea is a tubular structure that forms part of the lower respiratory tract. The trachea is continuous superiorly with the larynx and inferiorly becomes the bronchial tree within the lungs. The trachea consists of a support frame of semicircular, or C-shaped, rings made out of hyaline cartilage and reinforced by collagenous connective tissue. Trachea: Anatomy, and lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy by the end of the stage.

Embryonic layers

Process of development at the embryonic stage

The bronchial tree Bronchial tree The collective term “bronchial tree” refers to the bronchi and all of their subsequent branches. The bronchi are the airways of the lower respiratory tract. At the level of the 3rd or 4th thoracic vertebra, the trachea bifurcates into the left and right main bronchi. Both of these bronchi continue to divide into secondary or lobar bronchi that bifurcate further and further. Bronchial Tree: Anatomy develops off of the foregut Foregut Development of the Abdominal Organs of the embryonic gut tube.

• Occurs 4–7 weeks after conception
• Embryonic gut tube:
  • Forms from the laterally folded endoderm Endoderm The inner of the three germ layers of an embryo. Gastrulation and Neurulation layer 
  • Is surrounded by mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation
  • Has 3 sections:
    • Foregut Foregut Development of the Abdominal Organs
    • Midgut Midgut Development of the Abdominal Organs
    • Hindgut Hindgut Development of the Abdominal Organs
• Lung bud (respiratory diverticulum Diverticulum A pouch or sac opening from the colon. Diverticular Disease):
  • Buds off of the ventral side of the foregut Foregut Development of the Abdominal Organs around week 4
  • Simultaneously grows out (ventrally) and down (caudally)
  • Includes both endoderm Endoderm The inner of the three germ layers of an embryo. Gastrulation and Neurulation and surrounding splanchnopleuric mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation
• Tracheoesophageal groove (or ridge):
  • As the lung bud grows out and down, the tracheoesophageal groove appears as lateral indentations between the new lung bud and the foregut Foregut Development of the Abdominal Organs.
  • The grooves/ridges move in medially, “pinching off” the lung bud, and forming the tracheoesophageal septum.
  • The tracheoesophageal septum creates two separate tubes:
    • Esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy (posteriorly, from the original foregut Foregut Development of the Abdominal Organs)
    • Trachea Trachea The trachea is a tubular structure that forms part of the lower respiratory tract. The trachea is continuous superiorly with the larynx and inferiorly becomes the bronchial tree within the lungs. The trachea consists of a support frame of semicircular, or C-shaped, rings made out of hyaline cartilage and reinforced by collagenous connective tissue. Trachea: Anatomy (anteriorly, from the lung bud) 
• Primary bronchial buds: The trachea Trachea The trachea is a tubular structure that forms part of the lower respiratory tract. The trachea is continuous superiorly with the larynx and inferiorly becomes the bronchial tree within the lungs. The trachea consists of a support frame of semicircular, or C-shaped, rings made out of hyaline cartilage and reinforced by collagenous connective tissue. Trachea: Anatomy bifurcates into the right and left bronchial buds.
• Defects at this stage can cause:
  • Tracheoesophageal fistula Fistula Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. Anal Fistula (TEF): occurs when the tracheoesophageal grooves fail to fully close in the midline 
  • Esophageal atresia Atresia Hypoplastic Left Heart Syndrome (HLHS): portions of the esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy fail to form; often coexists with TEF
  • Tracheal atresia Atresia Hypoplastic Left Heart Syndrome (HLHS): partial or complete absence of the trachea Trachea The trachea is a tubular structure that forms part of the lower respiratory tract. The trachea is continuous superiorly with the larynx and inferiorly becomes the bronchial tree within the lungs. The trachea consists of a support frame of semicircular, or C-shaped, rings made out of hyaline cartilage and reinforced by collagenous connective tissue. Trachea: Anatomy below the larynx Larynx The larynx, also commonly called the voice box, is a cylindrical space located in the neck at the level of the C3-C6 vertebrae. The major structures forming the framework of the larynx are the thyroid cartilage, cricoid cartilage, and epiglottis. The larynx serves to produce sound (phonation), conducts air to the trachea, and prevents large molecules from reaching the lungs. Larynx: Anatomy (lethal): The lower respiratory tract is often connected to the GI tract.
  • Bronchopulmonary sequestration: abnormally formed nonfunctioning accessory lung tissue that is not connected to the rest of the bronchial tree Bronchial tree The collective term “bronchial tree” refers to the bronchi and all of their subsequent branches. The bronchi are the airways of the lower respiratory tract. At the level of the 3rd or 4th thoracic vertebra, the trachea bifurcates into the left and right main bronchi. Both of these bronchi continue to divide into secondary or lobar bronchi that bifurcate further and further. Bronchial Tree: Anatomy

Pseudoglandular Stage

This stage generates most of the bronchial tree Bronchial tree The collective term “bronchial tree” refers to the bronchi and all of their subsequent branches. The bronchi are the airways of the lower respiratory tract. At the level of the 3rd or 4th thoracic vertebra, the trachea bifurcates into the left and right main bronchi. Both of these bronchi continue to divide into secondary or lobar bronchi that bifurcate further and further. Bronchial Tree: Anatomy. It gets its name because histologically, the bronchi Bronchi The larger air passages of the lungs arising from the terminal bifurcation of the trachea. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into bronchioles and pulmonary alveoli. Bronchial Tree: Anatomy (which are lined with cuboidal cells at this stage) resemble glands as they branch into the surrounding mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation.

• Occurs at weeks 5–16 after conception
• At the beginning of this stage, around week 5, the lung bud and primary bronchial buds have formed.
• During this stage, continued distal budding Budding Mycology/branching of the bronchi Bronchi The larger air passages of the lungs arising from the terminal bifurcation of the trachea. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into bronchioles and pulmonary alveoli. Bronchial Tree: Anatomy forms a majority of the respiratory tree.
• Secondary bronchial buds:
  • Right bronchial bud trifurcates into 3 secondary lobar bronchial buds.
  • Left bronchial bud bifurcates into 2 secondary lobar bronchial buds.
• Tertiary bronchial buds: continued division
  • Right lung: approximately 20 tertiary bronchi Bronchi The larger air passages of the lungs arising from the terminal bifurcation of the trachea. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into bronchioles and pulmonary alveoli. Bronchial Tree: Anatomy
  • Left lung: approximately 18 tertiary bronchi Bronchi The larger air passages of the lungs arising from the terminal bifurcation of the trachea. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into bronchioles and pulmonary alveoli. Bronchial Tree: Anatomy
• Terminal bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy: extensive branching (approximately 20 divisions take place) down to the level of terminal bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy
  • Terminal bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy (with thick epithelial linings) develop.
  • Respiratory bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy do not develop until the next stage→  no gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange is possible → fetus cannot survive yet
• Branching bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy invade the surrounding mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation.
• Mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation is differentiating into:
  • Pulmonary vasculature → pulmonary capillary network begins to form
  • Connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology
  • Bronchial muscles
  • Cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology
• Pneumocyte precursors begin to develop:
  • Undifferentiated cuboidal epithelial cells line the respiratory tree.
  • Produce amniotic fluid Amniotic fluid A clear, yellowish liquid that envelopes the fetus inside the sac of amnion. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (amniocentesis). Placenta, Umbilical Cord, and Amniotic Cavity
• The first breathing movement can be seen as early as 10 weeks of gestation.
  • Breathing is controlled by the brainstem.
  • Breathing movements are paradoxical: the diaphragm Diaphragm The diaphragm is a large, dome-shaped muscle that separates the thoracic cavity from the abdominal cavity. The diaphragm consists of muscle fibers and a large central tendon, which is divided into right and left parts. As the primary muscle of inspiration, the diaphragm contributes 75% of the total inspiratory muscle force. Diaphragm: Anatomy contracts and the thorax moves inwardly, and vice versa.
• By the end of this stage:
  • Formation of terminal bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy, an arterial system, cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology, and smooth muscle
  • Pneumocyte precursors develop.
• Defect at this stage:
  • Bronchial atresia Atresia Hypoplastic Left Heart Syndrome (HLHS) or stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS)
  • Bronchogenic cyst Bronchogenic Cyst A usually spherical cyst, arising as an embryonic out-pouching of the foregut or trachea. It is generally found in the mediastinum or lung and is usually asymptomatic unless it becomes infected. Imaging of the Mediastinum: anomalous budding Budding Mycology of the foregut Foregut Development of the Abdominal Organs that does not communicate with the tracheobronchial tree

Canalicular Stage

During this stage, the respiratory units (also referred to as canaliculi) develop at the end of the terminal bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy.

• Occurs 16–26 weeks after conception
• Respiratory units begin to develop:
  • Terminal bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy (small “conducting” airways) extend and branch into the respiratory bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy.
  • Respiratory bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy lead to 3–6 alveolar ducts (the first primitive alveolar structures).
  • Vascularization of the surrounding mesenchyme occurs → dense capillary networks begin to surround the alveolar ducts
  • Fusion of the capillary and respiratory epithelial basement membranes
• Type II pneumocytes Type II pneumocytes Lungs: Anatomy:
  • Thicker cuboidal cells (unable to exchange gas) 
  • Line most of the respiratory epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology and alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS)
  • Begin producing surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) around week 20
  • Continue to produce amniotic fluid Amniotic fluid A clear, yellowish liquid that envelopes the fetus inside the sac of amnion. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (amniocentesis). Placenta, Umbilical Cord, and Amniotic Cavity
  • Minimal differentiation into flattened type I pneumocytes Type I pneumocytes Lungs: Anatomy that are capable of gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange
• Surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) (abbreviation for “surface active agent”):
  • Produced from glycogen
  • Consists of:
    • Lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids (made up mostly of phosphatidylcholine) 
    • Hydrophobic surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis B and C
    • Hydrophilic Hydrophilic Aminoglycosides surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis
  • Stored in lamellar bodies
  • Covers the alveolar surface
  • ↓ Surface tension Surface tension The force acting on the surface of a liquid, tending to minimize the area of the surface. Acute Respiratory Distress Syndrome (ARDS) within the alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) prevents collapse of the alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) after birth.
• By the end of the canalicular stage:
  • Some respiration Respiration The act of breathing with the lungs, consisting of inhalation, or the taking into the lungs of the ambient air, and of exhalation, or the expelling of the modified air which contains more carbon dioxide than the air taken in. Nose Anatomy (External & Internal) is possible owing to creation of the gas-exchanging portions of the lung.
  • A large part of the amniotic fluid Amniotic fluid A clear, yellowish liquid that envelopes the fetus inside the sac of amnion. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (amniocentesis). Placenta, Umbilical Cord, and Amniotic Cavity has been produced.
  • The maturity of the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy is based on production of surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS).
  • Infants born at the later stage can survive with intensive care. 
• Defects at this stage: cause damage to the gas-exchange components and result in structural alterations of the pulmonary parenchyma

Saccular Stage

During this stage, the alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) begin to mature, as type II pneumocytes Type II pneumocytes Lungs: Anatomy (cuboidal cells) flatten into type I pneumocytes Type I pneumocytes Lungs: Anatomy capable of gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange, creating the gas-exchange surface area. Surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) production increases significantly.

• Week 26 after conception through birth
• Alveolar ducts expand into terminal sacs and begin to mature:
  • Type II pneumocytes Type II pneumocytes Lungs: Anatomy (thick cuboidal cells incapable of gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange) → flatten into thin type I pneumocytes Type I pneumocytes Lungs: Anatomy (capable of gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange)
  • Results in thin-walled terminal sacs (immature alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS))
  • Type II pneumocytes Type II pneumocytes Lungs: Anatomy ↑ production of surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS): usually reach adequate levels around week 32
• Capillary networks grow:
  • Capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology associate with the terminal sacs.
  • Basal membrane forms between the pneumocytes in the terminal sacs and the endothelial cells. 
• Gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange becomes possible:
  • When maturing terminal sacs with thin type 1 Type 1 Spinal Muscular Atrophy pneumocytes associate with capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology
  • Known as the blood–air barrier
• By the end of the saccular phase:
  • All generations of the conducting and respiratory branches have been formed. 
  • Sacculi are thin, smooth-walled sacks capable of gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange.
  • Surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) production is increasing.
• Infants born > 32 weeks have a much ↑ chance of survival than those born at 24 weeks.

Alveolar Stage

During the alveolar stage, the respiratory units continue to grow in number and maturity.

• From 32 weeks after conception through 8 years of life
• Septation of terminal sacs → ↑ surface area and leads to further maturation of alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS)
• Continued expansion of the capillary network
• Alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) continue to increase in number:
  • 50 million alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) at birth 
  • Rapid ↑ in alveolar number in the 1st 6 months of life
  • Continued growth in number and size of alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) until age 8
  • Approximately 300 million alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) by age 8

Clinical Relevance

• Tracheoesophageal fistula Fistula Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. Anal Fistula: occurs when the esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy is connected to the trachea Trachea The trachea is a tubular structure that forms part of the lower respiratory tract. The trachea is continuous superiorly with the larynx and inferiorly becomes the bronchial tree within the lungs. The trachea consists of a support frame of semicircular, or C-shaped, rings made out of hyaline cartilage and reinforced by collagenous connective tissue. Trachea: Anatomy by a fistular tract: A tracheoesophageal fistula Fistula Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. Anal Fistula is commonly associated with esophageal atresia Atresia Hypoplastic Left Heart Syndrome (HLHS), though multiple different anatomic variations are possible. Management requires surgical correction.
• Pulmonary hypoplasia Hypoplasia Hypoplastic Left Heart Syndrome (HLHS): incomplete development of the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy, resulting in an abnormally low number or size of bronchopulmonary segments Bronchopulmonary segments Lungs: Anatomy and/or alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS): Pulmonary hypoplasia Hypoplasia Hypoplastic Left Heart Syndrome (HLHS) can be suspected on prenatal ultrasound with diagnosis at birth based on clinical findings and imaging and/or pulmonary testing. Management is focused on ventilatory support, and survival depends on the degree of lung underdevelopment.
• Neonatal respiratory distress syndrome Neonatal Respiratory Distress Syndrome Respiratory distress syndrome (RDS), also known as hyaline membrane disease, is caused by the lack of adequate pulmonary surfactant production in an immature lung. The syndrome is most commonly seen in preterm infants. Neonatal Respiratory Distress Syndrome: disease due to a deficiency of surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS) in a preterm infant due to the immaturity of the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy: This syndrome commonly occurs in infants < 28 weeks of gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care. Diagnosis is usually clinical, with characteristic findings on chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests. Management includes prevention of preterm labor Preterm labor Preterm labor refers to regular uterine contractions leading to cervical change prior to 37 weeks of gestation; preterm birth refers to birth prior to 37 weeks of gestation. Preterm birth may be spontaneous due to preterm labor, preterm prelabor rupture of membranes (PPROM), or cervical insufficiency. Preterm Labor and Birth, maternal steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors to promote fetal lung maturity while still in utero, giving surfactant Surfactant Substances and drugs that lower the surface tension of the mucoid layer lining the pulmonary alveoli. Acute Respiratory Distress Syndrome (ARDS), and providing respiratory support. 
• Respiratory physiology: Human cells rely primarily on aerobic metabolism. Therefore, obtaining oxygen from the environment and bringing it to the tissues while excreting the byproduct of cellular respiration Respiration The act of breathing with the lungs, consisting of inhalation, or the taking into the lungs of the ambient air, and of exhalation, or the expelling of the modified air which contains more carbon dioxide than the air taken in. Nose Anatomy (External & Internal) (carbon dioxide) in the most efficient manner is required for survival.